Human hepatocyte and kidney cell metabolism of 2-acetylaminofluorene and comparison to the respective rat cells
β Scribed by Robert Langenbach; Kenneth Rudo
- Publisher
- Springer
- Year
- 1988
- Tongue
- English
- Weight
- 789 KB
- Volume
- 4
- Category
- Article
- ISSN
- 0742-2091
No coin nor oath required. For personal study only.
β¦ Synopsis
The metabolism and mutagenic activation of 2-acetylaminofluorene by human and rat hepatocytes and kidney cells were measured. High performance liquid chromatography was used to separate the 2-aeetylaminofluorene metabolites, and a cell-mediated Salmonella typhimurium mutagenesis assay was used to detect mutagenic intermediates. Rat and human differences were observed with cells from both organs and levels of metabolism and mutagenesis were higher in human cells. Within a species, liver and kidney cell differences were also evident, with levels of hepatocyte-mediated metabolism and mutagenesis being greater than kidney cells. Human inter-individual variation was apparent with cells from both organs, but the variation observed was significantly greater in hepatoeytes than kidney cells. A knowledge of such differences, including an understanding that they may vary with the chemical being studied, shouM be useful in the extrapolation of rodent carcinogenesis data to humans.
π SIMILAR VOLUMES
Monolayers of rat hepatocytes metabolize 0.25 mM 2acetylaminofluorene (AA F) to various ether-extractable, watersoluble as well as covalently bound products. The major ether-extractable metabolite formed is 2-aminofluorene (AF), followed by 7-OH-AAF and 9-OH-AAF. Pretreatment of rats with the induce
## Abstract Primary cultures of human hepatocytes and hepatoma cell line HepG2 are frequently used to evaluate the hepatic disposition of drugs and other xenobiotics. To check the variability of the expression of drugβmetabolizing enzymes in these in vitro models, expression of genes coding for sev